Introduction: For women with advanced ovarian cancer survival outcomes with standard cytotoxic chemotherapy are poor and are thought to reflect the existence of drug-resistant ovarian cancer stem cells. TRX-E-002-1 (Cantrixil), a novel third generation benzopyran molecule has been shown to be effective in a mouse model of recurrent chemotherapy-resistant ovarian cancer. We present the final results of a phase I progressive design trial (Part A dose escalation, Part B dose expansion) of Cantrixil (NCT02903771). The objectives were to establish maximum tolerated dose (MTD) when given in combination with chemotherapy, and to evaluate safety, tolerability and anti-tumour activity of intraperitoneal (IP)-administered Cantrixil. Methods: Women who had completed ≥2 prior regimens and whose disease was platinum-refractory, platinum-resistant or who had documented intolerance to platinum therapy, were eligible. Treatment comprised up to eight 3-week cycles. In the first 2 cycles, patients were dosed weekly with Cantrixil as monotherapy after which investigators were allowed to initiate pre-defined standard intravenous chemotherapy regimens (cycles 3-8). All patients were followed up for 3 months after the end of treatment. Results: Of 32 patients enrolled, 25 received ≥1 Cantrixil dose; 6 patients (24%) completed all 8 treatment cycles. Patients (92% Caucasian, mean age 62.5 years) had a median of 2 prior lines of platinum therapy and a median of 3 prior lines of anticancer therapies (including anti-VEGF; n=13, 52% and PARPi; n=6, 24%). Platinum sensitivity: refractory (n=3,12%), resistant (n=17, 68%), sensitive (n=5, 20%). In Part A (n=11), an MTD of 5mg/kg was established on the dose-limiting toxicity of ileus (n=2) and safety signals of bowel obstruction (n=3) and abdominal pain (n=2). The pharmacokinetic profile was multi-exponential, with rapid increases in systemic concentration and distribution and a slower elimination phase. Drug accumulation was minimal and was not influenced by co-administration of chemotherapy. Analysis of weight and dose-normalized (to 1 mg/kg) data found no notable trends. Across Parts A and B, 16 patients received ≥1 Cantrixil dose and had a post-baseline efficacy measurement available. The overall response rate was 18%, including one complete response (platinum-resistant; who remains in remission 37.05 months since starting treatment) and two partial responses (one platinum-resistant, one platinum refractory). The median progression free survival was 3.06 months (95% CI:1.28,∞). Conclusion: IP-administered Cantrixil, a first-in-class, dual acting, anti-cancer therapy has encouraging activity in a cohort of difficult to treat patients with persistent epithelial ovarian, fallopian tube or primary peritoneal cancer who have demonstrated resistance to a range of prior treatments. Disease response compares favorably to a figure of 10% for historical controls.

Citation Format: Jermaine Coward, Ganessan Kichenadasse, Paul Harnett, Kathleen Moore, Minal Barve, James Garner, Mary Lopresti, Don S. Dizon. TRX-E-002-1 in treatment-refractory ovarian cancer: Final phase 1 study results from the dose-escalation and dose-expansion cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT012.